Receptor binding of fluorinated histidine analogs of thyrotropin-releasing hormone in various regions of the rat brain

Vonhof, Stefan; Paakkari, Ilari; Feuerstein, Giora; Cohen, Louis A.; Labroo, Virender M.

doi:10.1016/0014-2999(89)90233-1

Cited by 19 publications

(3 citation statements)

References 28 publications

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“…TRH has multiple biological effects at various anatomical sites which may be mediated via different TRH receptor subtypes (22)(23)(24)(25). Previously, we have observed that backbone thionation of enkephalins yielded receptor-selective analogs (12,15).…”

Section: Resultsmentioning

confidence: 99%

Biological activities of thionated thyrotropin-releasing hormone analogs

Łankiewicz

Bowers

Reynolds

et al. 1992

Biochemical and Biophysical Research Communications

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SUMMARY:Analogs of thyrotropin-releasing hormone (Glp-His-Pro--NH2, TRH) have been prepared which contain thioamide moieties in the pyroglutamic acid ring, the carboxyamide proline terminus, andin both positions (dithio). These compounds have been tested für TSH-releasing activities (in vitro and in viuo), and for binding to TRH receptors in rat pituitary and cortex. The monothionated analoge showed no significant differences in TSH-releasing potency from TRH either in vitro or in vivo. However, with two thioamide replacements the potency decreases about 50%. Significantly, in terms of receptor selectivity, thionation has resulted in differentiation between brain receptors (p~tuitary and cortex). The Pro'V[CSNH2) and dithio analogs were more selective (higher affinity to pituitary receptors) than the parent hormone, while the analog containing a thioamide replacement in the pyroglutamyl ring had lower affinity and was not selective. These results suggest that the subtle exchange of sulphur for oxygen can have an important impact on both receptor selectivity and affinity within 8 biologically active peptide. 0 1992 Academic Press, Inc.

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Section: Resultsmentioning

confidence: 99%

Biological activities of thionated thyrotropin-releasing hormone analogs

Łankiewicz

Bowers

Reynolds

et al. 1992

Biochemical and Biophysical Research Communications

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“…[20][21][22][23] The molecular docking analysis reveals a second binding site of TRH-DE, which is surrounded by Tyr527, Phe522, Pro269, Phe956, Met406, Tyr403, Gln266, Ser268, Met957, Pro402, Ala239, Ile241, Arg950, Ile236, Thr949, Asn238, Tyr237, Lys146, Glu953, Lys274, Gly952, His271, Leu955 and Asp519 amino acid residues (Fig. 15).…”

Section: Computational Studies Of Peptide 8c With Trh-dementioning

confidence: 98%

“…The synthesized analogs bind to TRH-R2 with slightly higher affinity than TRH-R1 and displayed selective activation for TRH-R2. 22,23 Simultaneous replacement of the central histidine in TRH by leucine or norvaline and the terminal amino acid pGlu by other heterocycles led to the identification of RGH-2202 (posatirelin), which is 5 times more CNS potent than TRH with weaker hormonal activity. Several studies involving this analog reported improved cognitive and functional abilities for late onset of Alzheimer's disease and RGH-2202 is currently in phase III clinical trial as a cognition enhancer.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of CNS active thyrotropin-releasing hormone (TRH)-like peptides: Biological evaluation and effect on cognitive impairment induced by cerebral ischemia in mice

Meena

Thakur

Nandekar

et al. 2015

Bioorganic & Medicinal Chemistry

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Synthesis of imidazo[4,5‐c]pyridines with a trifluoromethyl group at C‐4 and/or C‐6

Gautam¹,

Fujii²,

Nishida³

et al. 1994

Journal of Heterocyclic Chem

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Thermal condensation of histamine with trifluoroacetaldehyde gives 4‐(trifluoromethyl)spinacamine and subsequent dehydrogenation with selenium dioxide leads to 4‐(trifluoromethyl)‐1H‐imidazo[4,5‐c]pyridine (42%). Fluorination with sulfur tetrafluoride of L‐spinacine, obtained from the condensation of L‐histidine with formaldehyde, affords 6‐(trifluoromethyl)spinacamine, which can be converted to 6‐(trifluoromethyl)‐1H‐imidazo[4,5‐c]pyridine with selenium dioxide (49%). Application of the sequential reactions to 4‐(trifluoro‐methyl)‐L‐spinacine gives 4,6‐bis(trifluoromethyl)‐1H‐imidazo[4,5‐c]pyridine. Dehydrogenation of the tetrahydropyridine ring also occurred during the fluorination with sulfur tetrafluoride.

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Receptor binding of fluorinated histidine analogs of thyrotropin-releasing hormone in various regions of the rat brain

Cited by 19 publications

References 28 publications

Biological activities of thionated thyrotropin-releasing hormone analogs

Biological activities of thionated thyrotropin-releasing hormone analogs

Synthesis of CNS active thyrotropin-releasing hormone (TRH)-like peptides: Biological evaluation and effect on cognitive impairment induced by cerebral ischemia in mice

Synthesis of imidazo[4,5‐c]pyridines with a trifluoromethyl group at C‐4 and/or C‐6

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